The Phenolic Signature of <scp> <i>Psidium cattleianum</i> </scp> Fruits and Leaves Modulates <scp>TRPV1</scp> and <scp>TRPA1</scp> Transient Receptor Potential Channels: A Metabolomics, In Vitro, and In Silico Study

Although <i>Psidium cattleianum</i> (strawberry guava, Myrtaceae) is known for its anti-inflammatory, antioxidant, antimicrobial, and antidiabetic properties, its phytochemical profile and associated bioactivities remain largely underexplored. This study employed UHPLC-QTOF-HRMS for untargeted phenolic profiling of leaf and fruit extracts from <i>P. cattleianum</i>, followed by semi-quantification of phenolic subclasses and multivariate data analysis. Four hundred sixty-nine metabolites, including various phenolic subclasses-predominantly flavonoids and phenolic acids were- identified and annotated. Using HEK-293 cells stably transfected with TRPA1 or TRPV1 cation channels, it was found that both leaf and fruit extracts activate and rapidly desensitize TRPA1 in a concentration-dependent manner (EC₅₀ 18 and 30 μg/mL; IC₅₀ 60 and 47 μg/mL, respectively). Additionally, molecular docking analysis provided deeper insights into the interactions between <i>P. cattleianum</i> phytochemicals and the TRPA1 cation channel, identifying theaflavin 3,3'-<i>O</i>-digallate as the phenolic compound with the highest affinity (S score of -9.27 Kcal/mol). Interestingly, except for theaflavin 3,3'-<i>O</i>-digallate, compounds enriched in the leaf extract exhibited weaker binding interactions and lower S scores (approximately -7 Kcal/mol) compared to those enriched in the fruit extract. Also, a 100 ns molecular dynamics study of theaflavin 3,3'-<i>O</i>-digallate with TRAP1 demonstrated high binding stability of the complex. Overall, this study offers valuable insights into the phytochemical characteristics of <i>P. cattleianum</i> extracts and reveals their mechanism of action through affinity for the TRPA1 cation channel-receptors.